Further evidence that extracellular serotonin in the rostral ventrolateral medulla modulates 5-HT(1A) receptor-mediated attenuation of exercise pressor reflex.

We determined changes in extracellular levels of glutamate, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) within rostral ventrolateral medulla (RVLM) during 5-HT(1A)-receptor stimulation-mediated inhibition of cardiovascular responses to static muscle contraction using anesthetized rats. In ten rats, muscle contraction significantly increased (P<0.01) mean arterial pressure (MAP) by 29+/-4 mm Hg, heart rate (HR) by 25+/-3 bpm, and glutamate levels by 4.5+/-0.8 ng/5 microl. Microdialysis of a 5-HT(1A) receptor agonist, 8-OH-DPAT (10 mM), into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effect on glutamate levels. A subsequent administration of 10 mM WAY100635, a 5-HT(1A) antagonist, into the RVLM antagonized the attenuating effects of 8-OH-DPAT. In another ten rats, muscle contraction significantly increased (P<0.01) MAP and HR by 20+/-2 mmHg and 25+/-8 bpm, respectively. In addition, levels of 5-HT, NE, and DA in the RVLM significantly increased (P<0.01) by 3.6+/-0.3, 3.2+/-0.3, and 3.3+/-0.4 pg/10 microl, respectively. Administration of 8-OH-DPAT (10 mM) into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effects on NE and DA levels. However, the drug significantly attenuated 5-HT levels following a muscle contraction. Microdialysis of 10 mM WAY100635 into the RVLM reversed both cardiovascular and 5-HT changes. These results suggest that stimulation of 5-HT(1A)-receptors within the RVLM attenuates cardiovascular responses to static exercise via a reduction of extracellular 5-HT concentration and most likely not through changes in glutamate, NE or DA levels.

Modulation of extracellular glutamate and pressor response to muscle contraction during NMDA-receptor blockade in the rostral ventrolateral medulla.

Recently our laboratory demonstrated increases in extracellular glutamate concentrations within the rostral ventrolateral medulla (RVLM) during static muscle contraction (Caringi, D.C., Maher, T., Chaiyakul, P., Asmundsson, G., Ishide, T., Ally, A. Pflügers Arch. Eur. J. Physiol., 435:465-471, 1998). In this study, we determined effects of microdialyzing D(-)2-amino-7-phosphonohepatanoic acid (AP-7), an NMDA-receptor antagonist, into the RVLM on changes in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate levels during muscle contraction in anesthetized rats. Bilateral placements of microdialysis probes into the RVLM were verified by perfusing L-glutamate and obtaining a pressor response. Muscle contraction for 2 min, increased MAP and HR by 22+/-4 mmHg and 28+/-5 bpm, respectively. Extracellular glutamate as determined by microdialysis increased from 0.8+/-0.2 to 6.3+/-1.2 ng/5 microl. Microdialysis of AP-7 (1.0 microM) for 30 min inhibited contraction-evoked MAP and HR responses (10+/-3 mmHg and 13+/-3 bpm) and attenuated increases in glutamate during muscle contraction. Developed tensions did not differ during contractions before and after AP-7. Results demonstrate that NMDA-receptor blockade in the RVLM inhibits cardiovascular responses during static muscle contraction via a reduction in extracellular glutamate levels.